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Table 5 Proposed regulators of VOC

From: Vascular ossification – calcification in metabolic syndrome, type 2 diabetes mellitus, chronic kidney disease, and calciphylaxis – calcific uremic arteriolopathy: the emerging role of sodium thiosulfate

Positive Regulators Negative Regulators
Minerals: Ca ++ Pi, Phosphate/Pit-1 → Cbfa-1 Fetuin-A
Vitamin D  
BMP-2 Bone morphogenic protein MGP Matrix gammacarboxyglutamate (Gla)-protein Inhibits BMP-2
Warfarin may also cause skin necrosis similar to CPLX via an impairment of Protein C with thrombosis in venules resulting in subcutaneous ischemia and Vitamin K – GLA inhibition. GLA gammacarboxyglutamate
Inflammation: TNFalpha, IL-6 IL-10
Oxidized – retained – modified lipids (OxLDL-C, OxVLDL beta lipoproteins) and Low alpha lipoproteins: HDL-C Osteopontin: OPN (may be a positive and negative regulator)
ROS Oxidative-Redox Stress Osteoprotegerin OPG? Elevated in human atherosclerosis and CVD yet paradoxically when you have a mouse model with knockout of OPG there is increased osteoporosis and VOC.
Hormones: Insulin, IGF-1, Amylin, Leptin, and PTH  
I or II Hyperparathyroidism  
HYPOXIA activates hypoxia inducible factor Hif-1, ROS → Vascular angiogenesis Vasa Vasorum: Multipotential → Pericyte RANK and RANKL These are involved but as with OPG the entire story is still evolving.